海南医科大学学报2025，Vol.31Issue(19)：1477-1487,11.DOI:10.13210/j.cnki.jhmu.20241217.002
重楼皂苷Ⅱ与反式肉桂醛调控ROCK/LIMK/cofilin通路抑制子宫腺肌病异位内膜细胞侵袭迁移的机制研究
Mechanism of polyphyllin Ⅱ and trans-cinnamaldehyde modulating the ROCK/LIMK/cofilin pathway to inhibit invasive migration of ectopic endometrial cells in uterine adenomyosis
摘要
Abstract
Objective:To investigate the mechanism of polyphyllin(PPⅡ)and trans-cinnamaldehyde(TCA)inhibiting the progression of adenomyosis(AM)through modulating the ROCK/LIMK/cofilin pathway.Methods:Human adenomyosis-de-rived cells(AMDC)were extracted and cultured,and the effects of gradient concentrations of polyphyllin Ⅰ,Ⅱ,Ⅶ(PPⅠ,PPⅡ,PPⅦ)and TCA on the viability of AMDC were detected using CCK-8 assay;the optimal ratio of PPⅡ to TCA(PT for short)was screened by orthogonal experiment;Transwell assay and immunofluorescence assay were used to detect the ability of PT to inhibit AMDC invasion and migration;Western blot was used to detect the protein expression levels of ROCK1,LIMK,p-LIMK,cofilin,and p-cofilin;graded concentrations of PT were injected intraperitoneally into ICR mice for 30 d.Hematoxylin-eo-sin staining(H&E)was used to observe the morphological changes in the liver,spleen,and kidney tissues of the mice,and en-zyme-linked immunosorbent assay(ELISA)was used to measure the activities of alanine aminotransferase(ALT),aspartate ami-notransferase(AST),alanine aminotransferase(ALP),and blood urea nitrogen(BUN)in serum.Tamoxifen was fed to the neo-natal ICR female mice to establish the AM model,as well as the blank control group,the model group,the low-dose group of PT,the high-dose group of PT,and the group of the positive compounded mifepristone group were set up,and administered drug-intervention for 30 d.Morphological changes in the mouse uterus were detected by H&E staining,and the expression levels of ROCK1,p-LIMK,p-cofilin,and KI67 in uterine tissues were detected by immunohistochemistry.Results:The results of in vitro experiments showed that PPⅡ and TCA were more effective in inhibiting AMDC viability;PT most significantly inhibited AM-DC invasion and migration(P<0.001),downregulated the protein expression of ROCK1,LIMK,p-LIMK,cofilin,and p-cofilin(P<0.05),and inhibited the cytoskeletal rearrangement of AMDC(P<0.001).The results of in vivo experiments showed that PT drug did not damage the liver,spleen,and kidney tissue morphology;did not affect serum ALP,BUN activity,and AST/ALT ratio;attenuated the number of endometrial glands invading the myometrium in AM model mice,and reduced the expression levels of ROCK1,p-LIMK,p-cofilin,and KI67 in uterine tissues of AM mice(P<0.05).Conclusion:PT can reduce the inva-sion of glands into the myometrium and delay the progression of AM by inhibiting the expression of ROCK/LIMK/cofilin pathway.关键词
子宫腺肌病/重楼皂苷Ⅱ/反式肉桂醛/ROCK/LIMK/cofilin通路Key words
Adenomyosis/Polyphyllin Ⅱ/Trans-cinnamaldehyde/ROCK/LIMK/cofilin pathway分类
医药卫生引用本文复制引用
曹涵,王子璐,王楚矗,石雅馨,师伟..重楼皂苷Ⅱ与反式肉桂醛调控ROCK/LIMK/cofilin通路抑制子宫腺肌病异位内膜细胞侵袭迁移的机制研究[J].海南医科大学学报,2025,31(19):1477-1487,11.基金项目
This study was supported by the National Natural Science Foundation of China(82474559) （82474559）
Science Innovation Development Joint Project of the Natural Science Foundation of Shandong Province(ZR2023LZY024) 国家自然科学基金资助项目(82474559) （ZR2023LZY024）
山东省自然科学创新发展联合基金资助项目(ZR2023LZY024) （ZR2023LZY024）
